There has been a lot written about using micro-dosing for buprenorphine induction especially now that fentanyl is such a common issue. As a matter of fact, the recent issue of JAM, Journal of Addiction Medicine, contained an article titled “Low Dose Initiation of Buprenorphine: A Narrative Review and Practical Approach,” dealing with this very issue. Another article in the same issue, “A Plea From People Who Use Drugs to Clinicians: New Ways to Initiate Buprehorphine Are Urgently Needed in the Fentanyl Era” emphasized the predicament of many people who use drugs (PWUD). I found both of these articles very compelling, and suggest that you take a look at them. This was also a common theme at the ASAM meeting in April. There were several presentations on alternative methods of buprenorphine/naloxone induction.
The changes of precipitated withdrawal are greater when fentanyl is present especially with the tradition method of induction which is usually 2-3 days of withdrawal followed by a maximum dose of 8 mg the first day. Then over the next couple of days, the dose is increased to 12-16 mg if necessary. Most clinicians these days rarely go above 16 mg. However, fentanyl, though short acting pharmacologically, is very lipophilic and is present in the body tissues much longer. Microdosing (also called the Bernese Method) has been utilized to try and overcome this hurdle. Probably some of you have tried it. There are variations on the micro dosing protocol, but basically very small doses of buprenorphine, for example 0.5 mg or even 0. 25 mg, are gradually used over several days while the full agonist is still on board. This gradually displaces the full agonist, but not in amounts enough to cause precipitated withdrawal. The key here is that the patient continues to use the full agonist until the buprenorphine dose is large enough that all mu receptors are occupied. Then the full agonist is discontinued with no withdrawal symptoms.
The second article, coming out of the Internal Medicine Program of the Yale School of Medicine, is a narrative review of the mechanism, rationale, and existing methods for performing buprenorphine low dose initiation. I will not go into the details of the process they outline here, but they do list four Guiding Principles for Low Dose Initiation. 1. Choosing the Appropriate Clinical Situation, 2. Initiating at a Low Buprenorphine Dose (0.2-0.5 mg), 3. Titrating the Dose Slowly, and 4. Continuing the Full Opioid Agonist, Even if Nonmedical. At the ASAM meeting, I spoke to several people who had tried microdosing, some successfully, some not. One concern was the availability of such low doses of buprenorphine. In some states, there may be regulations about buprenorphine formulations that make this strategy difficult (but regulations can be changed via advocacy). Also, several clinicians failed to have the patient maintain the full opioid agonist during the induction, a key point in the process.
Another alternate strategy to initiate buprenorphine is macro-dosing. In this case, the patient is usually in withdrawal, and the h igh doses of buprenorphine are used, such as 32 mg. The theory is that this large dose will displace the full agonist and fully bind to the unoccupied mu opioid receptors. However, this approach has a very limited literature on its use. More research is needed on both of these approaches.
A recent article by Howard Hassman et.al. reviewed cases of prison inmates being transitioned from methadone to buprenorphine. The authors did a retrospective chart review of all inmates admitted to a prison in Germany between March 2019 and May 2020. In some cases methadone was tapered and a traditional induction was done. However, in one case a patient on 80 mg of methadone was directly switched to buprenorphine by stopping methadone for one day and then giving 4 mg buprenorphine sublingually followed by an injection of 16 mg of depot buprenorphine. In Germany, the weekly depot formulation is available. He was maintained on this dose weekly for 5 months and then switched to sublingual buprenorphine. He was also on 125 mg of gabapentin. In another case, a patient on 110 mg of methadone was given a 4 mg sublingual dose of buprenorphine after one day of withdrawal from methadone. He was then given 16 mg of a weekly depot formulation. He received another 8 mg buprenorphine sublingually the next day. He was stabilized on 32 mg of weekly depot formulation and eventually on 128 mg of a monthly formulation.
What these articles say to me is that we are missing many people who need to be on buprenorphine/naloxone, but aren’t for one reason or another. This is another case where we sometimes try to fit the patient to our available methods of treatment, rather than fitting the treatment to the patient. Here in Kentucky, we are somewhat limited by regulations guiding the use of MOUD. It is possible to change this. These articles suggest to me that we are missing the toughest patients. We may believe that access to medications for opioid use disorder are available. But we forget that some people still fall through the cracks, and they are the people who need it the most.
Cohen S, Weimer M, Levander X, Peckham A, Tetrault J, Morford K. Low Dose Initiation of Buprenorphine: A Narrative Review and Practical Approach. J Addict Med 2022;16 (4):399-406.
Sue K, Cohen S, Tilley J, Yocheved A. A Plea From People Who Use Drugs to Clinicians: New Ways to Initiate Buprenorphine are Urgently Needed in the Fentanyl Era. J Addict Med. 2022; 16(4): 389-391.
Howard Hassman, Stephanie Strafford, Sunita N. Shinde, Amy Heath, Brent Boyett, Robert L. Dobbins. (2022) Open-label, rapid initiation pilot study for extended-release buprenorphine subcutaneous injection. The American Journal of Drug and Alcohol Abuse 0:0, pages 1-10.